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Peripheral CD4 T follicular cells induced by a conjugated pneumococcal vaccine correlate with enhanced opsonophagocytic antibody responses in younger individuals.
Vaccine ( IF 5.5 ) Pub Date : 2020-01-03 , DOI: 10.1016/j.vaccine.2019.12.023
Sarah Sterrett 1 , Binghao J Peng 1 , Robert L Burton 1 , David C LaFon 1 , Andrew O Westfall 2 , Suddham Singh 3 , Michael Pride 3 , Annaliesa S Anderson 3 , Gregory C Ippolito 4 , Harry W Schroeder 5 , Moon H Nahm 5 , A Krishna Prasad 3 , Paul Goepfert 5 , Anju Bansal 1
Affiliation  

BACKGROUND PCV13 (conjugated polysaccharide) and PPSV23 (polysaccharide only) are two licensed vaccines targeting S. pneumoniae. The role of CD4 T-cell responses in pneumococcal vaccines among healthy participants and their impact on antibodies is not yet known. METHODS Ten adults (5 old and 5 young) received PCV13 (prime) and a year later PPSV23 (boost). Blood samples were collected prior to and multiple time points after vaccination. CD4 T cells responding to CRM197, polysaccharide (PS), CRM197 conjugated polysaccharide (CPS), PCV13 and PPSV23 vaccines were measured by flow cytometry. Serum antibodies were analyzed via multiplex opsonophagocytosis (MOPA) and pneumococcal IgG assays. RESULTS Vaccine-specific CD4 T cells were induced in all ten vaccinees post PCV13. Older vaccinees mounted higher peak responses and those specific for PCV13 and conjugated PS-1 were more polyfunctional compared to the younger group. Vaccine-elicited peripheral T follicular helper (Tfh) cells were only detected in the younger group who also exhibited a higher fold change in OPA titers post both vaccines. Importantly, Tfh cells following PCV13 correlated only with PCV13 serotype specific OPA titers after PPSV23 vaccination. CONCLUSIONS These findings demonstrate age related differences in immune response and the potential importance of Tfh in modulating functional antibody responses following pneumococcal vaccination.

中文翻译:

结合的肺炎球菌疫苗诱导的外周CD4 T滤泡细胞与年轻个体中增强的调理吞噬抗体反应相关。

背景技术PCV13(缀合多糖)和PPSV23(仅多糖)是靶向肺炎链球菌的两种许可疫苗。尚不清楚健康参与者中肺炎球菌疫苗中CD4 T细胞反应的作用及其对抗体的影响。方法十名成人(5岁,5名年轻)接受PCV13(初免),一年后接受PPSV23(增强)。在疫苗接种之前和之后的多个时间点采集血样。通过流式细胞术测量对CRM197,多糖(PS),CRM197结合多糖(CPS),PCV13和PPSV23疫苗有应答的CD4 T细胞。血清抗体通过多重调理吞噬作用(MOPA)和肺炎球菌IgG分析进​​行分析。结果在PCV13后所有十种疫苗中均诱导了疫苗特异性CD4 T细胞。与年轻组相比,年龄较大的疫苗具有更高的峰响应,而针对PCV13和结合PS-1的特异性更高。仅在较年轻的组中检测到疫苗引起的外周T滤泡辅助细胞(Tfh),它们在两种疫苗后的OPA滴度也显示较高的倍数变化。重要的是,接种PPSV23后,PCV13之后的Tfh细胞仅与PCV13血清型特异性OPA滴度相关。结论这些发现证明了肺炎球菌疫苗接种后免疫应答中年龄相关的差异以及Tfh在调节功能性抗体应答中的潜在重要性。仅在较年轻的组中检测到疫苗引起的外周T滤泡辅助细胞(Tfh),它们在两种疫苗后的OPA滴度也显示较高的倍数变化。重要的是,接种PPSV23后,PCV13之后的Tfh细胞仅与PCV13血清型特异性OPA滴度相关。结论这些发现证明了肺炎球菌疫苗接种后免疫应答中年龄相关的差异以及Tfh在调节功能性抗体应答中的潜在重要性。仅在较年轻的组中检测到疫苗引起的外周T滤泡辅助细胞(Tfh),它们在两种疫苗后的OPA滴度也显示较高的倍数变化。重要的是,接种PPSV23后,PCV13之后的Tfh细胞仅与PCV13血清型特异性OPA滴度相关。结论这些发现证明了肺炎球菌疫苗接种后免疫应答中年龄相关的差异以及Tfh在调节功能性抗体应答中的潜在重要性。
更新日期:2020-01-04
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